AUTHOR=Chandra Srijita , Cezar Guilherme , Rupasinghe Kinath , Magalhães Edison , Silva Gustavo S. , Almeida Marcelo , Crim Bret , Burrough Eric , Gauger Phillip , Madson Darin , Thomas Joseph , Zeller Michael , Zhang Jianqiang , Main Rodger , Rovira Albert , Thurn Mary , Lages Paulo , Corzo Cesar , Sturos Matthew , VanderWaal Kimberly , Naikare Hemant , Matias-Ferreyra Franco , McGaughey Rob , Retallick Jamie , McReynolds Sara , Gebhardt Jordan , Pillatzki Angela , Greseth Jon , Kersey Darren , Clement Travis , Christopher-Hennings Jane , Thompson Beth , Perkins Jonah , Prarat Melanie , Summers Dennis , Bowen Craig , Boyle Joseph , Hendrix Kenitra , Lyons James , Werling Kelli , Arruda Andreia G. , Schwartz Mark , Yeske Paul , Murray Deborah , Mason Brigitte , Schneider Peter , Copeland Samuel , Dufresne Luc , Boykin Daniel , Fruge Corrine , Hollis William , Robbins Rebecca , Petznick Thomas , Kuecker Kurt , Glowzenski Lauren , Niederwerder Megan , Huang Xiaoqiu , Linhares Daniel C. L. , Trevisan Giovani TITLE=Harnessing sequencing data for porcine reproductive and respiratory syndrome virus (PRRSV): tracking genetic evolution dynamics and emerging sequences in US swine industry JOURNAL=Frontiers in Veterinary Science VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1571020 DOI=10.3389/fvets.2025.1571020 ISSN=2297-1769 ABSTRACT=Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important swine pathogen affecting the United States of America (USA), leading to significant economic losses. Despite advances in diagnostic testing, there remains a gap in understanding the genetic evolution of PRRSV, especially in tracking the emergence of novel sequences and their spread across different regions and production stages. This research addresses this gap by developing a systematic methodology for directly collecting and analyzing PRRSV ORF5 sequences from veterinary diagnostic laboratories. The study aimed to identify trends among collected sequences and emerging PRRSV sequences by integrating nucleotide sequence data with metadata, providing critical insights into their geographic distribution, collected specimens, swine age groups, lineages, variants, and restriction fragment length polymorphism (RFLP) patterns. As of December 2024, the database housed 115,643 PRRSV ORF5 sequences. Sublineages 1B, 1A, 1H, and 1C.5 were the major wild-type PRRSV sequences detected over time, whereas vaccine-like strains comprised mostly of sublineages 5A and 8A. A novel sequence detection system was implemented, categorizing sequences based on similarity thresholds, ambiguities, and length criteria, identifying 167 novel sequences for the period between 2010 and 2024, whereas only three had continued detection in the field over time, forming clusters of detection. The analysis of these novel sequences highlighted significant trends, including the dominance of grow-finish animals in sequence origin and the high number of detections of sublineage 5A. Production sites located in states with the largest swine inventory have contributed to the most frequent detection of new PRRSV strains. Additionally, the development of a web-based tool provides end users with the capability to search sequences similar to their query sequence, providing macroepidemiological information and genetic sequence features to support PRRSV management and control. Real-time PRRSV sequencing data analysis informs producers and veterinarians of any upcoming novel sequences and trends of detection. The findings are intended to enhance current surveillance efforts and support more effective strategies for managing PRRSV outbreaks, ultimately safeguarding animal health, economic sustainability in the swine industry, and ultimately contributing to national food production sovereignty through pork-derived products.